Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription

Journal Article · Thu Aug 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.15.6523· OSTI ID:5822746

Montgomery, K F; Tarr, P I; Bomsztyk, K; Harlan, J M; Pohlman, T H ^[1]; Osborn, L; Hession, C; Tizard, R; Goff, D; Vassallo, C; Lobb, R ^[2]

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1. Univ. of Washington, Seattle (United States)
2. Biogen, Inc., Cambridge, MA (United States)

Leukocyte adherence to endothelium is in part mediated by the transient expression of endothelial-leukocyte adhesion molecule 1 (ELAM-1) on endothelial surfaces stimulated by tumor necrosis factor {alpha} (TNF), interleukin (IL) 1, or bacterial lipopolysaccharide (LPS). The intracellular factors controlling induction of ELAM-1 mRNA and protein are unknown. In nuclear runoff experiments with cultured human umbilical vein endothelial cells (HUVEC), the authors demonstrate that transcriptional activation of the ELAM-1 gene occurs following stimulation with TNF. Sequence analysis of the 5{prime} flanking region of the ELAM-1 gene reveals consensus DNA-binding sequences for two known transcription factors, NF-{kappa}B and AP-1. Gel mobility shift assays demonstrate that TNF, IL-1, or LPS induces activation of NF-{kappa}B-like DNA binding activity in HUVEC. Phorbol 12-myristate 13-acetate, a known activator of protein kinase C (PKC), weakly induces NF-{kappa}B-like activity, ELAM-1 mRNA, and ELAM-1 surface expression in HUVEC. However, TNF, IL-1, and LPS do not activate PKC in HUVEC at doses that strongly induce NF-{kappa}B-like protein activation and ELAM-1 gene expression. PKC blockade with H7 does not inhibit activation of these NF-kB-like proteins but does inhibit ELAM-1 gene transcription. They conclude that PKC-independent activation of NF-{kappa}B in HUVEC with TNF, IL-1, or LPS is associated with, but not sufficient for, activation of ELAM-1 gene transcription.

• OSTI ID: 5822746
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:15; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
DNA SEQUENCING
PHORBOL ESTERS
BIOLOGICAL EFFECTS
TRANSCRIPTION FACTORS
GENE REGULATION
CHEMICAL ACTIVATION
ENDOTHELIUM
INFLAMMATION
LEUKOCYTES
MAN
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARCINOGENS
ESTERS
MAMMALS
MATERIALS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PRIMATES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
SYMPTOMS
TISSUES
VERTEBRATES
550200* - Biochemistry